Process for affecting molecules in tissue

ABSTRACT

A process for affecting molecules in neurological or neuromuscular tissue and cells and subcellular structures in the tissue of a host organism. The process includes introducing particles into the living cells of the tissues and thereby affecting the relative dipole moment and producing direct effects on subcellular structures and molecules in the cells of the tissues. A constant magnetic field can be applied to the tissue to enhance the dipole moment in the neurological or neuromuscular tissue and in their cells, or to enhance the effect of an alternative electromagnetic field applied to the tissue.

This is a division of copending application Ser. No. 6/886,616, filedJuly 18, 1986, which issued Mar. 21, 1989 as U.S. Pat. No. 4,813,399.

INTRODUCTION

The treatment of neurological or neuromuscular disorders currently islimited to chemotherapy and various surgical approaches. The use ofdrugs is limited because of side-effects and the blood-brain barrier.Various drugs are used to affect neurotransmission to the extent thateven neurotransmitters are used. The ability to control neurological orneuromuscular disorders with drugs is very limited and in many cases themechanisms are not completely understood. In addition the ability tocontrol the development and regeneration of nervous tissues as well asother tissues has not been achieved prior to this present invention.

BACKGROUND OF THE INVENTION

Diseases which affect the neurological system are multiple and consistof inflammatory lesions, conduction problems, and neurotransmissiondisorders. Different processes affect central nervous tissue vs.peripheral nervous tissue, myelinated nerve fibers vs. unmyelinatednerve fibers, and neurons themselves vs. glial cells and supportingcells. Most neurological diseases can only be very minimally treatedbecause of the inaccessability of nervous tissue. Examples includeamyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis,Parkinson's disease, spinal cord problems i.e. diabetic neuropathy andretropathy, etc. Disorders of embryogenesis and development ofneurological tissue as well as other tissues occur quite frequently anduntil the present invention there are very few methods of attempting tocontrol this process. Developmental disorders are characterized byspinal cord malformations (i.e. spina-bifida, etc.) and cerebralmalformations (hydrocephalous, etc.). Malignancies of the neurologicalsystem are also at present difficult to manage and extremely common inthe developmental stages.

The present invention seeks to overcome this problem by modifying theintracellular environment in the neural and supporting cells to controlthe disease process.

OBJECT OF THE INVENTION

The present invention seeks to control the function of neurologicaltissue by the use of intracellular particles which are present, capableof being induced or introduced and the use of an alternatingelectromagnetic field to affect these particles and consequently theneurological tissue. Through the introduction of intracellular energythe function of the neuron as well as the conduction of the impulse canbe controlled. A constant magnetic field can be used to impart a dipoleto the particles prior to treatment with the alternating electromagneticfield to enhance the effect. In addition the constant magnetic field canbe used to modify the behavior of the neural cells and to modulate thedisease process or conduction mechanism.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an electrical circuit analogous to nerve activation.

FIG. 2 is an illustration of a nerve terminal full of synaptic vessiclesand mitochondria.

DETAILED DESCRIPTION OF THE INVENTION

The use of particles to alter the energy level in the cell by theabsorption of electromagnetic energy by the particle has been disclosedin the Applicant's U.S. Pat. Nos. 4,106,488; 4,136,683; 4,303,636; and4,359,453. The present invention seeks to use particles to affect theabsorption of energy by the cell itself and in particular by neuralcells in the tissue. The implementation of this present treatment methodin part utilizes inventive aspects which are the subject of otherapplications for U.S. Letters Patent by the same inventor as recitedhereinafter. For example, a fuller understanding of the technologyunderlying the Gordon treatment reveals the operation of subtlemechanisms which can themselves become a contributing factor in thecourse of treatment and are incorporated herein by reference. Theselection of particle compositions for use in this present invention asdisclosed in the applicant's above described U.S. Patents and asdisclosed in copending and commonly assigned applications, Ser. Nos.418,298; 464,870 including C.I.P. 522,941, including C.I.P. 535,390, nowU.S. Pat. No. 4,662,359; 524,844, now U.S. Pat. No. 4,590,922; and561,811 as well as application No. 627,536 of the same inventor, areincorporated herein by reference.

Below several MHz the transmission of energy directly to the cell by anexternal alternating electromagnetic field is affected by thecharacteristics of the cell membrane. The charge accumulation on themembrane from intracellular and extracellular fluids accounts for thedielectric polarization of the membrane. The intracellular andextracellular electrolyte solution accounts for the conductance.

In the prior Gordon U.S. Pat. Nos. 4,303,636; 4,106,488; and 4,359,455,a high frequency magnetic field is employed to have a direct effect onthe particles so that diseased cells can be killed by thermal effectsdue to hysteresis loss from the particles themselves when the field isrelaxed. The particles of the present invention are utilized to alterthe behavior of neuronal cells and supporting cells.

Through the introduction of particles in the nerve cells theintracellular conductivity can be altered as well as the chargeaccumulation on the cell membrane. The alteration in cell membranecharacteristics enables the delivery of energy intracellularly at alower frequency due to the effect of the charge accumulation on the cellmembrane and the increased conductivity of the nerve cell allows moreenergy to be delivered and a better coupling at the given frequency.

Mechanical, chemical, thermal stimuli as well as electrical can activatea nerve. Activation consists of initiation of an action potential withan alteration of ion permeability and the corresponding ion flexes. Ananalogous electrical circuit is described in FIG. 1. Obviously anychange inside the cell will affect membrane polarization and conduction.

Synapses occur as connections between nerves and between nerves andother tissues. An example is the neuromuscular junction where the nerveending is connected to the end plate of the muscle fiber. The nerveterminal is full of synaptic vesicles and mitochondria. This isillustrated in FIG. 2.

The neurotransmitters are often released at nerve endings or atsynapses. Examples are acetylcholine or nor-epinephrine.

Iron is taken up quite well by certain areas of the brain. In certainpathological conditions increased or different accumulations of iron canoccur. The blood brain barrier prevents the passage of most proteinsinto the brain. However, the capillaries in the brain have demonstratedtransferrin receptors for the uptake of iron. These are the onlycapillary receptors for transferrin in the body. Therefore iron uptakein the brain occurs by endocytosis via a receptor mediated mechanism.Iron is demonstrated in oligodendrocytes, glial cells and neurons. Inaddition active neurons have an inherent magnetic field secondary totheir electric current. These magnetic fields can be monitored.

Neurons contain receptors. Transferrin receptors have been demonstratedon axons and dendrites. The ligand reaction with the receptor changesthe membrane potential and ionic conductance which changescharacteristics of nerves and causes transmitter release. An electricfield can also affect transmitter release.

The uptake of iron in the brain can be modulated by chemical means.Chloroquin which is lysosomotropic can decrease the uptake by neuronaland glial cells. This uptake can also be decreased by ammonium chlorideor methylamine. Iron accumulation in the brain is associated withneuromelanin, ceroid-lipofuscin and Hallervorden-Spatz syndrome.

The transport of iron particles and other particles in myelinated andunmyelinated fibers depends on the particle size and composition.Neurons take up iron particles by endocytosis. In unmyelinated nervesiron-dextran particles are transported along the unmyelinated pathwaysto the substantia nigra. After injection Fe-dextran is taken up by axonsand transported retrograde to cell bodies. (No toxicity from ironparticles in ganglion cell bodies of neuron).

Transport of the particles is extremely dependent on cell type andparticle size, composition and conformation. In myelinated nervesiron-dextran is transported to the cell bodies in 2-3 weeks at a rate of1-2 mm/day. However horse-radish peroxidase (HRP) is transported to thecell bodies in 20 hrs. at a rate of 2-3 mm/hour. Therefore differentparticles can be used to produce the effect in different areas. The irondextran is longer than HRP and achieves cell body localization at alater time.

Most ganglia cells (cell bodies) will demonstrate iron after the axonsare exposed to particles. In axons the iron dextran can cause swellingof myelin layers. The particles can embed in the myelin and react withit to decrease transport. However in the present invention theassociation of the particles with the myelin allows an affect to themyelin layers and the conduction in the axon. This is especially usefulin diseases affecting the myelination of nerves.

Oligodendrocytes have endogenous iron and avidly take up Fe-dextranparticles. This allows the ability to affect the function of thesupporting glial cells as well.

Therefore the nerves do take up and transport iron particles. Thepresent invention provides the ability to affect cells and metabolism innerves and neurons. The particles can also be directed to themitochondria of the axons and therefore affect the metabolic rate aswell as the conduction of the nerves. The presence of these particles inthe mitochondria at the nerve terminals in synapses or at neuromuscularjunction allows for control of neurotransmitter release and alsoneuromuscular function.

Unmyelinated fibers label quickly with iron-dextran particles and travelvia the nigrostriatal pathway to the thalamus and locus coeruleuspathway. This route can be used to affect central portions of the brainwith the present invention.

Retinal ganglion cells can be labeled by injection into the superiorcolliculus and the lateral geniculate nucleus. This allows for controlof the visual pathways. The dopaminergic neurons of the substantia nigraafter striatal injection can also be controlled. Different pathways alsotransport the particles at a different rate.

In certain circumstances unmyelinated fibers as in the nigrostratatalsystem transport faster than the myelinated visual system. This can bedue to the interaction of the particles with the myelin. This allows forcontrol of one pathway over another depending on the timing and type ofparticle utilized. The transport of iron-dextran is affected by theinteraction of the particles with the myelin and the uptake by the glialcells which decreases central transport. In thinly myelinated pathwaysas in the striatum-thalamus and thalamus-nucleus reticulous thalamipaths the transport of iron particles is faster due to the decrease ininteraction with the myelin. The fastest path for iron-dextran particlesis the unmyelinated paths i.e. dopaminergic nigro striatal pathway andthalamus-locus coeruleus moradrenergic path.

The process of the present invention involves the use of intracellularparticles to modify and modulate neuronal and glial cell function. Theseparticles may be introduced into the subject by intravenous,intraarterial, intralymphatic injection or injection into thecerebrospinal fluid. The particles may also be injected directly intothe neurological tissue or a specific pathway.

This process also applies to neurological tissue and other tissue duringdevelopment to modify the developmental process. The expression oftransferrin receptors for iron particles is extremely high during thisphase.

The particles are of a ferromagnetic, paramagnetic, or diamagneticnature and therefore capable of responding to an external alternatingelectromagnetic field. The particles, in general, are under 1 micron insize and in a colloidal-type suspension although for a direct injectionthey may be directly introduced.

In addition, any electric or magnetic dipole in the cell or capable ofbeing induced in the cell may be utilized. A constant magnetic field canbe used to induce these dipoles as well as enhance the effect of theexternal alternating electromagnetic field or dipoles or particlescontaining these dipoles which are present in the cell. This constantmagnetic field can be used to help maximize particle uptake andabsorption, and to help concentrate the particles in the desired area.

The choice of particle type, size and shape can be highly significant toeffective treatment, particularly where subcellular localization orother subtle differentiations in metabolic activity, for example, areconveniently utilized to maximize particle uptake and absorption.Different particles are chosen depending on the desired pathway orultimate area of nervous tissue which is desired to be affected asdescribed above. Suitable particles and exemplifications of selectionparameters are disclosed and examined in copending and commonly assignedApplication Ser. No. 535,390, now U.S. Pat. No. 4,662,359 of the sameinventor, incorporated herein by reference.

The particle systems include metalloporphyrins, Fe₂ O₃,metal-metalloporphyrins and particularly useful particle including bothinorganic elements and compounds as well as metal containing organiccompounds. Inorganic elements and compounds particularly well suited,owing to their favorable magnetic parameters, comprise elements such asdysprosium, erbium, europium, gadolinium, holmium, samarium, terbium,thulium, ytterbium or yttrium and compounds thereof such as dysprosiumsulfate, erbium sulfate, europium oxide, europium sulfate, gadoliniumoxide, gadolinium sulfate, holmium oxide, samarium sulfate, terbiumoxide, terbium sulfate, thulium oxide, ytterbium sulfide, yttrium oxide,yttrium sulfate, yttrium ferrioxide (Y₃ Fe₅ O₁₂), yttrium aluminum oxide(Y₃ Al₅ O₁₂), other dimetallic compounds such as dysprosium-nickel,dysprosium-cobalt, gadolinium-iron, ytterbium-iron, cobalt-samarium,gadolinium-yttrium, and dysprosium-gallium, and actinide series elementsand compounds thereof.

Metal containing-organic molecules useful for the application describedabove, comprise particles of iron-dextrans such as FeOOH-dextrancomplexes and other dextran metal complexes wherein the metal isselected from the group comprising cobalt, iron, zinc, chromium, nickel,gallium, platinum, manganese and rare earth metals such as dysprosium,erbium, europium, gadolinium, holmium, samarium, terbium, thulium,ytterbium and yttrium, other dimetallic compounds such asdysprosium-nickel, dysprosium-cobalt, gadolinium-iron, ytterbium-iron,cobalt-samarium, gadolinium-yttrium, and dysprosium-gallium and ironsuch as Fe₂ O₃ particles, Fe₃ O₄ particles and FeOOH particles and Fe₂O₃ -dextran complexes, Fe₃ O₄ -dextran complexes, and FeOOH-dextrancomplexes, and actinide series elements and compounds, ferric ammoniumcitrate, and various iron transporting and chelating compounds such asenterochelin, transferrin, etallothionein, hydroxamates, phenolates,ferrichromes, desferri-ferrichromes, ferritin, ferric mycobactins, andiron-sulfur proteins such as ferredoxin and rubredoxin and transferrinas well as transferrin compounds and complexes.

Particularly appropriate metal-containing organic structures for usewith the present invention are the porphyrins such as etioporphyrins,mesoporphyrins, uroporphyrins, coproprophyrins, protoporphyrins, anddicarboxylic acid containing porphyrins and substituted porphyrins suchas tetraphenylporphyrin sulfonate (TPPS). Especially advantageousprotoporphyrins comprise hematoporphyrins, chlorophylls, andcytochromes. In addition to the naturally occuring protoporphyrins whichpossess either iron or magneium containing moieties, mixed-metal ordi-metal hybrid porphyrins may also be prepared. For example, bysubstituting an alternative metal for the iron in hematoporphyrin, theadvantages of the porphyrin moiety (e.g., in terms of specificity oflocalization is retained while the unique magnetic properties of the newmetal enhance the sensitivity of the substituted molecule. Suitablemetals for purposes of substitution comprise cobalt, iron, manganese,zinc, chromium, gallium, nickel, platinum and rare earth series ofmetals such as dysprosium, erbium, europium, gadolinium holmium,samarium, terbium, thulium, ytterbium and ytterium, dimetallic compoundssuch as dysprosium-nickel, dysprosium-cobalt, gadolinium-iron,ytterbium-iron, cobalt-samarium, gadolinium-yttrium, dysprosium-galliumand actinide series elements and compounds thereof. The substitutedporphyrins are then optionally reacted with dextran to form ametal-containing porphyrin dextran complex in particle form. Suitableporphyrin acceptors comprise any dicarboxylic acid containing porphyrinsuch as protoporphyrins (e.g. hematoporphyrins) and the like.

The substitution reaction is carried out in vitro by reacting thedesired metal with the desired porphyrin in the presence of the enzymeferrochelatase (E.C. 4.11.1.1). Reaction conditions as described byJones and Jones (Biochem. J. 113: 507-14, 1969) or Honeybourne, et al(FEBS Lett.: 98: 207-10, 1979) are suitable.

Additional particle systems particularly suited to use in this presentinvention include Fe₄ O₄ -transferrin dextran, metal-transferrin(transition, rare-earth), metalloporphyrin-transferrin,antibody-ferritin-particles, antibody-ferritin-transferrin particles,antibody-transferrin particles, metalporphyrin-metal complexes,metallothionein particles, and lectin particles. Useful particle systemsfor use in this present invention further comprise: Where particle=Fe₃O₄, transition metal, rare-earth metal, metalloporphyrin, etc. as wellas ferromagnetic and paramagnetic particles.

One magnetic characteristic known to be temperature dependent ismagnetic susceptibility. Magnetic susceptibility is measured by theratio of the intensity of magnetization produced in a substance to themagnetizing force or intensity of the field to which it is subjected.This magnetic characteristic is routinely measured by magnetometerdevices such as a vibrating magnetometer or a flux gate magnetometer.Therefore, by measuring the magnetic susceptibility of particles atvarious temperatures, it is quite simple to calibrate the magnetometerequipment so that when it measures the magnetic susceptibility of theparticles a simple calibration will indicate the exact correspondingtemperature of the particle.

By way of illustrating the increased magnetic susceptibility of some ofthe elements or compounds described above, the following table isprovided:

    ______________________________________                                                          Temp                                                        Element or Compound                                                                             (K.)     Mag. Sus. (10.sup.6 cgs)                           ______________________________________                                        Iron Oxide (ref.) 293       +7,200                                            Dysprosium Oxide  287.2    +89,600                                            Dysprosium Sulfate Octahydrate                                                                  291.2    +92,760                                            Erbium Oxide      286      +73,920                                            Erbium Sulfate Octahydrate                                                                      293      +74,600                                            Europium          293      +34,000                                            Europium Oxide    298      +10,100                                            Europium Sulfate  293      +25,730                                            Holmium Oxide     293      +88,100                                            Holmium Sulfate Octahydrate                                                                     293      +91,600                                            Terbium           273      +146,000                                           Terbium Oxide     288.1    +78,340                                            Terbium Sulfate                                                               Octahydrates      293      +76,500                                            Thulium           291      +25,500                                            Thulium           296.5    +51,444                                            Ytterbium Sulfide 292      +18,300                                            ______________________________________                                    

Thus, the enhanced magnetic characteristics displayed by the particlesof the subject invention result in an increase in an electromagneticfield thereby increasing the overall sensitivity and control of themodalities for the improvement of the present invention techniques andfor the resultant effects.

Magnetic susceptibility has also been used heretofore in connection withthe treatment protocol as disclosed in U.S. Pat. No. 4,163,683 of thesame inventor, where magnetic susceptibility measurements are correlatedwith temperature (an interdependent variable) in accomplishing therelated induction heating step controllably. There is no recognition,however, that the values for magnetic susceptibility, independent of theinduction heating step or the imposition of an electromagnetic field canbe usefully correlated (to maximization of particle concentration withtime to optimize treatment effectiveness, as demonstrated herein.

A further benefit is derived from the fact that some particlecompositions comprise a ferromagnetic, paramagnetic, or diamagneticcomponent integrated into a cell or organelle specific molecularstructure, thereby permitting efficient targeting and delivery of saidparticles to specific intracellular compartments such as mitochondria,chloroplasts, nuclei, vacuoles, and the like.

In addition, particle systems which are kept outside the neural cellsmay be utilized to alter membrane events and affect the frequency ofresponse and the energy transmission of the diseased neuronal cells. Incertain circumstances these particles may be utilized to stabilize themembrane of normal neuronal cells and decrease their response to a fieldat a given frequency.

A steady magnetic or electric field may be used to enhance the uptake ofparticles by the neuronal cells as well as enhancing the membrane andcytoplasmic alterations which occur and are fully disclosed anddescribed in copending and commonly assigned Application Ser. No.535,390, now U.S. Pat. No. 4,662,359 of the same inventor incorporatedherein by reference. For example, the application of the localizedstatic magnetic or electric field may occur concurrently with theapplication of an alternating, oscillating or pulsed electromagneticfield. That is to say, the localized static magnetic or electric fieldmay be superimposed on the subject of interest while the alternating,oscillating or pulsed field is also being applied.

Temperature measurements are taken in living tissue of the host organismand correlating the temperature readings to the low frequency magneticfield causing alteration in dielectric properties and/or conductivityand/or frequency dependent dispersion curves. Once the temperature iscorrelated with these measurements, (dielectric properties, conductivityand frequency dependent dispersion curves) these measurements are thenmade along three axes at right angles to one another in the hostorganism from which a three dimensional temperature map of the body isproduced by restructuring them in a three dimensional temperature modelby computer processes well known in the art.

The frequency of the magnetic field is selected to enhance thedielectric properties, conductivity and electric dipoles of the neuronalcells and will vary depending upon the particles employed therein. Thefrequency, however, is adjusted so that thermal effects thereby obtainedare not due to hysteresis loss from the particles themselves but ratherthe alteration in conductibility, dielectric properties and electricdipoles of the neuronal cells that are brought about by the use of theparticles of the present invention. Generally, the range of frequenciesthat may be employed will be anywhere from about 1 Hz to about 500 MHz;1 Hz to about 100 MHz; 1 Hz to less than 13 MHz; 1 Hz to about 100 KHz;1 hertz up to less than 50 kilohertz and especially from about 10 hertzup to about less than 50 kilohertz as well as any frequency within theseranges or range of frequencies within the aforesaid ranges.

The present invention, therefore, will be practiced at the abovefrequencies and the copending applications incorporated herein byreference will give the person of ordinary skill in the art a disclosureof how to practice the present invention with the exception that thefrequencies described above will be employed in lieu of those utilizedin such copending applications.

To further illustrate the operation of this instant invention, thefollowing treatment scenario is provided.

Reference herein to tissue, organ or cell population is intended in itsmost embracive and comprehensive sense, referring in general to theregion of the host organism affected by the invasive abnormality, or thetreatment region, as the context requires.

The subject receives an intravenous injection or direct injection of acolloidally suspended particle such as iron porphyrin (FeTPPS₄) at adosage of 2-10 mg/kg. After a prescribed period of time which isdependent on the method of introduction of the particles i.e. after 24hours--14 days after intravenous injection and 20 hours--10 days afterdirect injection, the subject is exposed to an alternatingelectromagnetic field at a frequency of 1 Hz to 100 MHz in this case 500Hz for a period of approximately 10-20 minutes. The alternatingelectromagnetic field may be applied via a coil arrangement or viacapacitor plates or via electrodes in the tissue or any suitable meansavailable in the state of the art, and consistent in application to thispresent invention. The process may be repeated as is necessary.

This field supplies energy to the interior of the neuronal cells therebyaffecting only the reactive and/or diseased neuronal cells and not thenormal neuronal cells. The amount of energy can be precisely controlledto affect only the reactive and/or diseased neuronal cells and not thenormal neuronal cells.

In summary, the introduction and absorption of minute particles into theneuronal cells alters the intracellular environment and the chargeaccumulation on the membrane. Consequently, lower power levels may beused to transmit energy into the neuronal cells. Lower frequencies maybe used because of the alteration in membrane events and the effect onnormal cells is greatly reduced because of the above as well as thestate of the neuronal cell's membrane. In addition, modification can beperformed by using particles to alter the extracellular environment aswell. Ultrasound techniques are also enhanced.

In addition, since radio frequency fields can affect particles bycausing reversible or irreversible changes in the particles, i.e.magnetostrictive induced vibrations, by affecting the particles with analternating electromagnetic field in the range 1 Hz to 500 MHz eitherprior to or during treatment, the particles can be made more or lessresponsive to the field. This alternating field can produce acousticchanges in the particle and affect the neuronal cell and subcellularstructures. Ultrasound can be used.

As disclosed by the applicant in his U.S. Pat. No. 4,136,683 and asdisclosed in copending and commonly assigned application Ser. No.535,390, now U.S. Pat. No. 4,662,359 (C.I.P. to application Ser. No.522,941) of the same inventor and incorporated herein by reference, thispresent invention can be used to create a three-dimensional temperaturemap of the body. In addition, the measurements of these properties inthe manner described herein, allows one to follow the distribution ofthe particles in the body by following the change in the dielectricproperties, conductivity, and frequency dispersion curves both beforeand after ingestion of the particles.

Molecules in a neuronal cell can be affected if μB>kT (where μ is dipolemoment, B is the field strength, k is the Boltzman constant, and T isabsolute temperature). Consequently by introducing the particles andincreasing the relative dipole moment in the neuronal cell the directeffects on molecules in the neuronal cell can be enhanced even beyondthermal effects. Therefore, this present invention may directly affectthe molecules in the neuronal cell.

Through these processes the dielectric properties across the membranecan be affected including the stimulation and/or alteration of nerveimpulses and/or electrical events.

The ionic environment around the surface of the particle by becomingpolarized can produce increased dielectric properties as well. Inaddition, membrane effects with the anionic proteinaceious materialwhich accumulates around the neuronal cell can produce local effects.

When you have a mixture with different dielectric properties relaxationphenomenon will occur not at a single frequency, but over a wide rangeof frequencies. The curve is broadened due to interactions in themixture. Inclusion of material of low dielectric constant will lower thedielectric constant of the mixture. Therefore, the addition of particlesto the inside of the neuronal cells broadens the frequency response ofintracellular structures as compared to the other cells and structures.Particle geometry also affects the frequency response. Consequently, thepresence of the particles allows for a differential affect onsubcellular structures.

Through the use of magnetic susceptibility measurements as described inthe applicant's U.S. Pat. No. 4,136,683 and as disclosed in copendingand commonly assigned application Ser. No. 535,390, now U.S. Pat. No.4,662,390 No. 535,390 (C.I.P. to application Ser. No. 522,941) and asdisclosed in copending and commonly assigned application Ser. No.627,536 of the same inventor and incorporated herein by reference, theuptake of particles in the neuronal cells and glial cells can befollowed as a function of time. This may be used diagnostically toevaluate which neurons are affected by the disease process and byanalyzing which cells take up the particles. The magneticcharacteristics of the particle in the neuronal cell can be used to helpdiagnose which disease process is present in the neurological tissue.Magnetic mapping techniques can also be used.

The process of this present invention is further illustrated by thefollowing examples:

EXAMPLE I

A colloidal solution of Fe₃ O₄ -dextran-transferrin is prepared in aconcentration of 20 mg/cc in Rogers lactate. An intravenous injection of2 cc is performed slowly over a period of 5 minutes. Over the next 48-72hours, periodic measurements of magnetic susceptibility using a SQUIDmagnetometer as well as magnetic mapping measurements are performed.This allows identification of the neuronal cells which are involved, aswell as helping to determine the type of disease process and the pointin time of maximum uptake of the particles. At this time, the subject issubjected to the alternating electromagnetic field which destroys thereactive and/or inflammatory diseased cells in the tissue. Any diseasedneurological tissue in the body can be treated by this process.

EXAMPLE II

FeTPPS₄ -Chloride 20 mg/cc is injected into the cerebrospinal fluid.After 36 hours localization is achieved in the neurons and the area tobe treated is placed in a helical coil where an alternatingelectromagnetic field is applied. The field is applied for 3-4 minutesto achieve the alteration in cellular behavior and the disease processmodified.

EXAMPLE III

A colloidal solution of Fe₃ O₄ -dextran-transferrin is prepared in aconcentration of 20 mg/cc in Ringers lactate. 1 cc is injectedstereotactically into the nigrostriatal pathway. After 24 hourslocalization is achieved in the thalamus. An alternating electromagneticfield is then applied to modulate thalamic function.

EXAMPLE IV

A colloidal solution of Fe₃ O₄ -dextran-transferrin is prepared at aconcentration of 20 mg/cc and 1 cc is injected into a myelinated nerve.Interaction occurs between the particles and the myelin after 72 hours.An alternating electromagnetic field is then applied to affect themyelin of the nerve as well as the conduction system within the nerve.

What is claimed is:
 1. A process for affecting molecules in neurologicalor neuromuscular tissue and cells and subcellular structures in thetissue of a host organism, said process comprising the stepsof:introducing particles into the cells of living tissue to affect therelative dipole moment in the tissue; thereafter, applying a constantmagnetic field to the tissue and thereby enhancing the dipole moment inthe tissue; and after said introducing step, applying an alternatingelectromagnetic field to the tissue.
 2. The process of claim 1 whereinsaid constant magnetic field enhances the effect of said alternatingelectromagnetic field.
 3. The process of claim 1 wherein said applyingthe alternative magnetic field step is after said applying the constantmagnetic field step.